The use of drug delivery systems providing both slow release of drugs and specific targeting of drugs to the desired affected organs/systems in order to reduce systemic distribution and exposure of non-target organs has long been sought. One promising candidate has been phospholipid (PL) liposomes and their derivatives. Liposomes are small, spherical vesicles composed of phospholipids and consist of one or more lipid bilayers enclosing an aqueous interior. Liposomes can encapsulate both hydrophilic drugs (in the aqueous interior) and lipophilic drugs (in the lipid bilayer), and are thus highly suitable for drug delivery.
Phospholipid liposomes can serve as sustained-release or controlled-release drug depots, thus contributing to improvement in drug efficacy and allowing reduction in the frequency of dosing. By providing protection of both the entrapped drug and the biological environment, liposomes reduce the risks of drug inactivation and drug degradation. Since the pharmacokinetics of free drug release from the particles are different from directly-administered free drug, these carriers can be used to reduce toxicity and undesirable side effects.
Phospholipid liposomes can be prepared at a wide range of sizes (50-500 nm). Since in inflamed tissues, the intercellular space is enlarged from the normal distance of 50 nm to 100 nm, drug-carrying liposomes smaller than 100 nm are suitable for selective delivery of drugs to target systems.
Despite the advantages offered, there are some difficulties associated with using drug encapsulating liposomes. For example, liposomes have limited targeting abilities, limited retention and stability in circulation, potential toxicity upon chronic administration, and the inability to extravasate.
To circumvent the drawbacks of known nanoliposomes, we have used polymer-conjugated lipids (Po-Ls) for the formation of mixed lipid/Po-L nanoliposomes.